Cost-effectiveness of pneumococcal vaccination for prevention of invasive pneumococcal disease in the elderly: an update for 10 Western European countries.

Pneumococcal vaccine is effective in preventing invasive pneumococcal disease in adults >or=65 years of age, but it is not widely used in Western Europe. In this study, data from an earlier (1995) cost-effectiveness study on Belgium, France, Scotland, Spain, and Sweden are updated, and data on five new countries--Denmark, the UK (specifically, England and Wales), Germany, Italy and The Netherlands--are added. Epidemiological and economic variables specific for each country were used, and it was assumed that pneumococcal and influenza vaccines would both be administered during the same physician visit. In the base-case analyses, the cost-effectiveness ratios ranged from euro 9239 to euro 23,657 per quality-adjusted life-year. Because the incidence and mortality of invasive pneumococcal disease were underestimated in most countries, a country-by-country analysis was performed, assuming an incidence of 50 cases per 100,000 population and mortality rates of 20, 30 and 40%. For a mortality of 20%, the cost-effectiveness ratios ranged from euro 4,778 to euro 17,093, and for a mortality of 30%, they ranged from euro 3,186 to euro 11,395. Pneumococcal vaccination to prevent invasive pneumococcal disease in elderly adults was very cost-effective in all 10 countries. This evidence justifies the wider use of the vaccine in Western Europe.

Invasive pneumococcal disease in adults in North-Rhine Westphalia, Germany, 2001-2003.

A population-based survey of invasive pneumococcal disease (IPD) was conducted among adults in North-Rhine Westphalia, Germany. The study included 202 of the 386 hospitals in the region, together with the 27 microbiological laboratories that submitted reports of IPD in these hospitals to the National Reference Centre for Streptococci. The reports of 16 laboratories were comprehensively reviewed. Most (95.8%) IPD isolates were susceptible to penicillin G, but 14.5% were resistant to clarithromycin. Serotypes 14 (15.6%), 3 (9.3%), 4 (7.1%) and 7F (7.9%) were the most common. The serotype coverage of the 23-valent pneumococcal polysaccharide vaccine was 80.8%. During 2001-2003, the annual incidence of IPD, after correcting for laboratory and hospital under-reporting, was 16.2/100 000 in individuals aged >or= 65 years. In three university hospitals, blood cultures were obtained for only 37% of patients with community-acquired pneumonia, and fewer than one-third of such cultures were obtained in one hospital before antibiotics were prescribed, suggesting that the true incidence of IPD was closer to 50/100 000.

Influenza vaccination in 2000: recommendations and vaccine use in 50 developed and rapidly developing countries.

Influenza vaccination is becoming an increasingly important aspect of public health programs in developed and rapidly developing countries. In 2000, most of these countries had national recommendations to vaccinate elderly people and those with high-risk conditions. Levels of vaccine use, however, varied widely and several rapidly developing countries had higher levels than those seen in many developed countries. More than one-third of all influenza vaccinations occurred in countries outside North America, western Europe and Australia and New Zealand. With increasing vaccine use, all countries will be better prepared for the next pandemic. Nonetheless, those countries that use but do not produce influenza vaccine will find it difficult to obtain supplies of pandemic vaccine.

Pneumococcal vaccination and pneumonia: even a low level of clinical effectiveness is highly cost-effective.

Most studies of the cost-effectiveness of pneumococcal vaccination show very favorable cost-effectiveness ratios for preventing pneumococcal pneumonia, but they make the controversial assumption that vaccination is equally effective in preventing bacteremic (BPP) and nonbacteremic (NBPP) pneumonia. However, the results of our study showed that, compared with preventing BPP alone, the cost-effectiveness of pneumococcal vaccination increased substantially even when only a small proportion of additional cases of NBPP were prevented.

The Japanese experience with vaccinating schoolchildren against influenza.

BACKGROUND: Influenza epidemics lead to increased mortality, principally among elderly persons and others at high risk, and in most developed countries, influenza-control efforts focus on the vaccination of this group. Japan, however, once based its policy for the control of influenza on the vaccination of schoolchildren. From 1962 to 1987, most Japanese schoolchildren were vaccinated against influenza. For more than a decade, vaccination was mandatory, but the laws were relaxed in 1987 and repealed in 1994; subsequently, vaccination rates dropped to low levels. When most schoolchildren were vaccinated, it is possible that herd immunity against influenza was achieved in Japan. If this was the case, both the incidence of influenza and mortality attributed to influenza should have been reduced among older persons. METHODS: We analyzed the monthly rates of death from all causes and death attributed to pneumonia and influenza, as well as census data and statistics on the rates of vaccination for both Japan and the United States from 1949 through 1998. For each winter, we estimated the number of deaths per month in excess of a base-line level, defined as the average death rate in November. RESULTS: The excess mortality from pneumonia and influenza and that from all causes were highly correlated in each country. In the United States, these rates were nearly constant over time. With the initiation of the vaccination program for schoolchildren in Japan, excess mortality rates dropped from values three to four times those in the United States to values similar to those in the United States. The vaccination of Japanese children prevented about 37,000 to 49,000 deaths per year, or about 1 death for every 420 children vaccinated. As the vaccination of schoolchildren was discontinued, the excess mortality rates in Japan increased. CONCLUSIONS: The effect of influenza on mortality is much greater in Japan than in the United States and can be measured about equally well in terms of deaths from all causes and deaths attributed to pneumonia or influenza. Vaccinating schoolchildren against influenza provides protection and reduces mortality from influenza among older persons.

Cost-effectiveness of pneumococcal vaccination of older people: a study in 5 western European countries.

Pneumococcal vaccination of older persons is thought to be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection is uncertain. Because there is better evidence of vaccination effectiveness against invasive pneumococcal disease, we determined the cost-effectiveness of pneumococcal vaccination of persons aged > or =65 years in preventing hospital admission for both invasive pneumococcal disease and pneumococcal pneumonia in 5 western European countries. In the base case analyses, the cost-effectiveness ratios for preventing invasive disease varied from approximately 11,000 to approximately 33,000 European currency units (ecu) per quality-adjusted life year (QALY). Assuming a common incidence (50 cases per 100,000) and mortality rate (20%-40%) for invasive disease, the cost-effectiveness ratios were <12,000 ecu per QALY in all 5 countries. For preventing pneumococcal pneumonia, vaccinating all elderly persons would be highly cost-effective to cost saving. Public health authorities should consider policies for encouraging pneumococcal vaccination for all persons aged > or =65 years.

The burden of pneumococcal disease among adults in developed and developing countries: what is and is not known.

The burden of pneumococcal disease among adults in developed countries is neither widely known nor appreciated. The incidence of pneumococcal pneumonia is uncertain because a precise diagnosis cannot be obtained for most patients. Population-based data on invasive pneumococcal disease (e.g., bacteraemia and meningitis) suggest an annual incidence in all developed countries of > or =15-20 cases per 100,000 persons of all ages and > or =50 cases per 100,000 elderly adults (> or =65 years). In developing countries there are no population-based data on the burden of pneumococcal disease among adults. Studies of high risk groups, hospital-based studies, vaccine efficacy trials, extrapolations from surveillance of "native populations" in developed countries, and demographic studies in developing regions all suggest a high burden of disease. The broad variation in these estimates, however, indicates that better studies are needed. Increased use of pneumococcal vaccines among adults in all countries will depend on better scientific and public understanding of the burden of pneumococcal disease. In developing countries, intensive community-based studies of the impact of pneumococcal disease, or, alternatively, a "vaccine probe" approach, in which a population is vaccinated and the reduction in pneumonia is compared with that in a control population, could give more accurate estimates of the burden of disease and of the potential effectiveness of pneumococcal vaccination among adults.

The clinical effectiveness of pneumococcal vaccination: a brief review.

Randomized controlled trials have shown that pneumococcal polysaccharide vaccine is efficacious in preventing pneumococcal bacteraemia and pneumococcal pneumonia in young adults. Clinical trials in older adults, however, have been inconclusive, usually because the studies have been too small. Retrospective studies have shown that pneumococcal vaccination is approximately 50-80% effective in preventing invasive pneumococcal disease among older persons. Vaccination in this age group is also very cost-effective. These findings are the basis for the recent expansion of immunisation policies and the growth in vaccine use in many developed countries. Serologic and clinical studies, however, suggest that vaccine-induced protection declines after 3-5 years, leading to widespread concern about the need for routine revaccination. Because pneumococcal polysaccharide vaccine does not induce immunologic memory, the benefits of revaccination can also be expected to be relatively short-lasting. Alternative strategies of immunological priming of adults with pneumococcal conjugate vaccine followed by boosting with polysaccharide vaccine, or perhaps vaccination with one of the newer protein vaccines, should be considered. Because these new generation pneumococcal vaccines could provide a foundation of life-long protection against pneumococcal infection, their widespread use among adults could have an immense impact on public health worldwide.

Influenza vaccination in 29 countries. An update to 1997.

OBJECTIVE: This report updates for 1996 and 1997 our 2 earlier reports on the use of influenza vaccination in various countries. METHODS: Methods for obtaining information on influenza vaccine use from 1980 to 1995 in each country are described in our earlier reports. The current report includes data for 29 countries. RESULTS: Among 16 countries of Western Europe, vaccine use increased substantially in The Netherlands, Finland (1996) and in Ireland (1997). In the remaining 13 countries, vaccine use increased somewhat or remained the same. In the US, vaccine use increased steadily throughout the 1990s, reaching a level of 281 doses per 1000 population in 1997. In New Zealand, there was a substantial increase in 1997, while vaccine use remained relatively unchanged in Canada, Australia and Korea. In Japan and Singapore, little or no influenza vaccine was used. In 1997, 6 countries in Central Europe used modest amounts of influenza vaccine. Among all 29 countries, in 1997 all but 3 (the UK, Ireland and Denmark) had age-based recommendations for influenza vaccination. This changed in 1998 when the UK and Denmark recommended vaccination for persons > or = 75 years and > or = 65 years of age, respectively. Ireland is considering an age-based recommendation. Many countries provide reimbursement for influenza vaccination through national or social health insurance, at least for some recommended groups. In virtually all countries, however, many persons pay for vaccination themselves. The levels of vaccine use in different countries are not related to per capita healthcare spending. Instead, they reflect different levels of awareness of influenza as an important disease and the effectiveness of vaccination in its prevention. CONCLUSIONS: Influenza vaccination has continued to increase or has stabilised in most developed countries, and vaccine is also being used in several developing countries. In spite of much progress, however, the full benefits of influenza vaccination have yet to be achieved in any country.

Pneumococcal vaccination for older adults: the first 20 years.

During the 20 years following its licensure, pneumococcal vaccine has not been widely used. Although the vaccine was shown to be efficacious in South African gold miners, clinical trials of 'pneumonia vaccine' in older adults that have attempted to demonstrate vaccine efficacy in preventing pneumonia have been inconclusive. Retrospective studies have convincingly demonstrated the effectiveness of vaccination in preventing invasive pneumococcal disease, but these findings have only gradually gained acceptance, largely because some observers reject the findings of observational studies or fail to appreciate the importance of invasive disease. In the 1980s, pneumococcal vaccine was used only in the US, but other countries began vaccination in the mid-1990s, in part due to a better understanding of the disease and the vaccine, but also because of concern about antimicrobial resistance. With greater understanding of the global importance of pneumococcal disease and the promise of conjugate and protein vaccines, during the next 20 years pneumococcal vaccines will become the most important vaccines for adults and children worldwide.

Measuring protection: efficacy versus effectiveness.

In the clinical development of a vaccine, an efficacy study asks the question, "Does the vaccine work?" In contrast, an effectiveness study asks the question "Does vaccination help people?". In general, vaccine development proceeds from a study of immunogenicity to a randomized controlled trial that determines vaccine efficacy under ideal conditions. Efficacy studies, however, have several limitations. In an immunogenicity study, when a vaccine is given according to different schedules, the object of the study is not the vaccine itself but the schedules; i.e., what is important is not the "relative immunogenicity" of the vaccine, but which schedule is more protective given the occurrence of the disease that is to be prevented. Furthermore, a clinical trial of vaccine efficacy is unable to predict accurately the level of protection that will be achieved in public health practice. Vaccination effectiveness can be evaluated in a prospective clinical trial, although few such studies have been undertaken. Effectiveness is usually assessed retrospectively, sometimes using a screening test, but more often in a case-control or cohort study. In these studies, rigorous risk adjustment is necessary to ensure the comparability of study populations. Retrospective studies also provide a means for assessing serious but rare vaccine-associated adverse events, an undertaking often needed to maintain public confidence in vaccination programmes. Many vaccines currently under development will be replacement rather than new vaccines, and they are unlikely to be evaluated in traditional efficacy trials. In future years, effectiveness studies, some of them using large administrative databases, will become increasingly important features of vaccine development and the formulation of public policy for immunization.

Pneumococcal vaccination in the United States and 20 other developed countries, 1981-1996.

This survey describes patterns of pneumococcal polysaccharide vaccine use, vaccine registration, vaccination recommendations, and reimbursement for vaccination in the United States and 20 other developed countries during the period 1981 through 1996. The United States was the only country to use appreciable amounts of the vaccine throughout the study period. Annual vaccine use was staple from 1982 through 1990 but then increased sharply. In the 20 other countries, very little pneumococcal vaccine was used until the 1990s, when new registrations and/or national recommendations were followed by dramatic increases in vaccine use in Iceland (1991), the United Kingdom (1994), Sweden (1995), and Norway, Belgium, and the province of Ontario in Canada (1996). In 1996, pneumococcal vaccine was still not licensed in three and not recommended in four of the 21 countries. Of the seven countries that used the most pneumococcal vaccine, public reimbursement for vaccination was provided in the United States, Canada, and the United Kingdom but not in Iceland, Sweden, Norway, or Belgium.

Cost-effectiveness of vaccination against pneumococcal bacteremia among elderly people.

CONTEXT: Clinical, epidemiologic, and policy considerations support updating the cost-effectiveness of pneumococcal vaccination for elderly people and targeting the evaluation only to prevention of pneumococcal bacteremia. OBJECTIVE: To assess the implications for medical costs and health effects of vaccination against pneumococcal bacteremia in elderly people. DESIGN: Cost-effectiveness analysis of pneumococcal vaccination compared with no vaccination, from a societal perspective. SETTING AND PARTICIPANTS: The elderly population aged 65 years and older in the United States in 3 geographic areas: metropolitan Atlanta, Ga; Franklin County, Ohio; and Monroe County, New York. MAIN OUTCOME MEASURES: Incremental medical costs and health effects, expressed in quality-adjusted life-years per person vaccinated. RESULTS: Vaccination was cost saving, ie, it both reduced medical expenses and improved health, for all age groups and geographic areas analyzed in the base case. For people aged 65 years and older, vaccination saved $8.27 and gained 1.21 quality-adjusted days of life per person vaccinated. Vaccination of the 23 million elderly people unvaccinated in 1993 would have gained about 78000 years of healthy life and saved $194 million. In univariate sensitivity analysis, the results remained cost saving except for doubling vaccination costs, including future medical costs of survivors, and lowering vaccination effectiveness. With assumptions most unfavorable to vaccination, cost per quality-adjusted life-year ranged from $35 822 for ages 65 to 74 years to $598 487 for ages 85 years and older. In probabilistic sensitivity analysis, probability intervals were more narrow, with less than 5% probability that the ratio for ages 85 years and older would exceed $100000. CONCLUSIONS: Pneumococcal vaccination saves costs in the prevention of bacteremia alone and is greatly underused among the elderly population, on both health and economic grounds. These results support recent recommendations of the Advisory Committee on Immunization Practices and public and private efforts under way to improve vaccination rates.

Influenza vaccination in 22 developed countries: an update to 1995.

This study expands and updates through 1995 our earlier report on influenza vaccine use in 18 developed countries. Five of the six countries with high levels of vaccine use in 1992 (> or = 130 doses/1000 population) showed little change or slight declines over the subsequent 3 years. The exception was the United States, where a new federal program for vaccination reimbursement for the elderly helped to increase vaccine distribution from 144 to 239 doses/1000 population. The six countries with medium levels of vaccine use in 1992 (76-96 doses/1000 population) increased to > or = 100 doses/1000 population by 1995. Among the six low-use countries in 1992 (< or = 65 doses/1000 population), only Finland showed substantial improvement (96 doses/1000 population) in 1995. Four new countries were added to the study. In Germany, vaccine use increased to 80 doses/1000 population in 1995, but in Ireland it remained at a low level (48 doses/1000 population). In Korea, vaccine use increased from 17 to 95 doses/ 1000 population during the period 1987-1995. In Japan, very high levels of vaccine use (approximately 280 doses/1000 population) in the early 1980s were associated with vaccination programs for school children. However, vaccine use fell precipitously when these programs were discontinued, and only 2 and 8 doses/1000 population were used in 1994 and 1995, respectively. In all 22 countries, higher levels of vaccine use were associated with vaccination reimbursement programs under national or social health insurance and were not correlated with different levels of economic development. Excluding Japan, in 1995 there was still a greater than fourfold difference between the highest and lowest levels of vaccine use among the other 21 countries in the study. Given its well established clinical effectiveness and cost-effectiveness, none of these countries has yet achieved the full benefits of its programs for influenza vaccination.